Complexation products of sodium tartrate with iron trichloride

Endpoint summary

Description of key information

The oral and dermal LD50 value of the test substance was > 2000 mg/kg body weight. The 4 hr LC50 was > 5.64 mg/L. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 July 2010 - 09 August 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: Crl:WI (Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: approx. 8-12 weeks old
- Weight at study initiation:Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: yes, overnight prior to dosing and until 3-4 hours after administration of the test substance
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material and paper as cage-enrichment.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period:at least 5 days before start of treatment under laboratory conditions


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±3
- Humidity (%): 40-70
- Air changes (per hr): approx.15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: 19 July 2010 - 02 Augustus 2010

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: Dose volume (mLlkg body weight) is calculated as follows: Dose level (g/kg) / spec.gravity or density (g/ml). Animals were given 1-2 ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Based on anticipated absence of toxicity at 2000 mg/kg.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2000 mg/kg: two group of 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. Weighing: Days 1 (pre-administration), 8 and 15 and at death (if found dead after Day 1).
- Necropsy of survivors performed: yes
- Other examinations performed: none.

Statistics:

Not applicable.

Preliminary study:

Not applicable

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortalities

Clinical signs:

Clinical signs observed during the study period were as follows:
Dose level Clinical signs
2000 mg/kg Hunched posture, piloerection on day 1

Body weight:

The mean body weight gain shown by the animals at 2000 mg/kg over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.

Gross pathology:

No further abnormalities were found at macroscopic post mortem examination of the animals.

Other findings:

None.

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The oral LD50 value of the test substance was > 2000 mg/kg body weight.

Executive summary:

Assessment of acute oral toxicity with Complexation products of sodium tartrate with iron trichloride in the rat (Acute Toxic Class Method).

The study was carried out based on the guidelines described in:

OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method"

Commission Regulation (EC) No 440/2008, B1 tris: "Acute Oral Toxicity, Acute Toxic Class Method"

EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity"

JMAFF guidelines (2000) including the most recent partial revisions.

Complexation products of sodium tartrate with iron trichloride was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg body weight, taking into account the purity of the test substance (35%). Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred.

Hunched posture and/or piloerection was observed for all animals on Day 1. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of Complexation products of sodium tartrate with iron trichloride in Wistar rats was established to exceed 2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 March 2012 and 08 May 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was performed according to OECD guideline and GLP. There were no significant deviations.

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Principles of method if other than guideline:

1. The relative humidity (animal room) increased above the target values on two separate occasions during the course of the study.
2. Two samples are outside 20% (Lower) of the mean achieved atmosphere concentration.
These deviations did not influence the outcome of the study.

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd, Oxon, UK
- Age at study initiation: eight to twelve weeks
- Weight at study initiation: 200g to 350g
- Fasting period before study: No
- Housing: The animals were housed in groups of five by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes (Datesand Ltd., Cheshire, UK) and provided with environmental enrichment items: wooden chew blocks and cardboard "fun tunnels" (Datesand Ltd., Cheshire, UK).
- Diet/water (e.g. ad libitum): With the exception of the exposure period, free access to mains drinking water and food (Harlan 2014C Rodent Diet, Harlan Laboratories UK Ltd, Oxon, UK) was allowed throughout the study. The diet, drinking water, bedding and chew blocks are routinely analysed and are considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of
the study.
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.62 - 22.42°C
- Humidity (%): 38.27 -77.98%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: see attached picture.
- Exposure chamber volume: 30 litres (dimensions: 28 cm diameter x 50 cm high).
- Method of holding animals in test chamber: During the day of exposure, each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber '0' ring. Only the nose of each animal was exposed to the test atmosphere.
- Source and rate of air: Compressed air. The chamber flow rate was maintained at 60 L/min providing 120 air changes per hour.
- Method of conditioning air: Compressed air was supplied by means of an oil free compressor and passed through a water trap and respiratory quality filters before it was introduced to the nebuliser.
- System of generating particulates/aerosols: glass concentric jet nebuliser (Radleys, Saffron Walden, Essex, UK) located at the top of the exposure chamber. The nebuliser was connected to a plastic syringe (covered in foil to protect the test item from light) attached to an infusion pump, which provided a continuous supply of test item formulation under pressure, and to a metered compressed air supply.
- Method of particle size determination: The particle size of the generated atmosphere inside the exposure chamber was determined three times during the exposure period using a Marple Personal Cascade Impactor (Westech IS Ltd, Beds., UK).
- Treatment of exhaust air: The extract from the exposure chamber passed through a 'scrubber' trap and was connected with a high efficiency filter to a metered exhaust system.
- Temperature, humidity, pressure in air chamber: The temperature and relative humidity inside the exposure chamber were measured by an electronic thermometer/humidity meter (Hanna Instruments Ltd, Beds., UK) located in a vacant port in the animals' breathing zone of the chamber and recorded every thirty minutes throughout the four-hour exposure period.

TEST ATMOSPHERE
- Brief description of analytical method used: HPLC was used. During the characterisation phase of the study the test atmosphere was sampled twice and filter samples were then submitted for chemical analysis to determine if the original test item was similar to the composition of the airborne test item.
Prior to the inhalation phase of the study, the non-volatile component of the test item was determined by adding a small, known amount of test item to glass fibre filters and recording their weights. The filters were then dried in a desiccator between 19 and 21°C for approximately 24 hours and then weighed again. The difference in the two weights was taken as the volatile content of the test item and the non-volatile component was calculated as a percentage. The mean non-volatile component of the batch used during the formal exposure was found to be 21.52% (n=10).
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
Cascade impactor data:
Impactor Stage Cut Point Amount Collected (mg) per Sample Number
Number (µm) 1 2 3 Mean Amount Collected (mg)
3 9.7 0.01 0.07 0.02 0.03
4 6.7 0.07 0.10 0.11 0.09
5 3.8 0.45 0.69 0.38 0.51
6 1.8 0.66 0.77 0.52 0.65
7 0.94 0.56 0.74 0.47 0.59
8 0.46 0.13 0.13 0.09 0.12
Back-up Filter<0.46 0.04 0.00 0.00 0.01
Total Mean Amount of Test Item Collected 2.00


Calculation
Cut Point Log10 Mean Cumulative Amount Less Than Cut Point
(µm) Cut Point (mg) (0/0) Probit
9.7 0.987 1.97 98.5 7.17
6.7 0.826 1.88 94.0 6.56
3.8 0.580 0.37 68.5 5.48
1.8 0.255 0.72 36.0 4.64
0.94 -0.027 0.13 6.50 3.49
0.46 -0.337 0.01 0.500 2.42

- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.47/1.92

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5.64 mg/L

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical Signs
All animals were observed for clinical signs at hourly intervals during exposure, immediately on removal from the restraining tubes at the end of exposure, one hour after termination of exposure and subsequently once daily for up to fourteen days. Any evidence of overt toxicity was recorded at each observation.
Bodyweight
Individual bodyweights were recorded on arrival, prior to treatment on the day of exposure and on Days 1, 3, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed:
Necropsy
At the end of the fourteen day observation period the animals were killed by intravenous overdose of sodium pentobarbitone. All animals were subjected to a full external and internal examination, and any macroscopic abnormalities were recorded. The respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.64 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality occured

Clinical signs:

other: Signs of hunched posture and pilo-erection are commonly seen in animals for short periods on removal from the chamber following 4-Hour inhalation studies. Wet fur is commonly recorded both during and for a short period after exposure. These observations a

Body weight:

All males and four female animals exhibited bodyweight losses on the first day postexposure. All male animals subsequently exhibited reasonable bodyweight gains throughout the remainder of the recovery period. In contrast, three female animals .exhibited slight bodyweight losses or showed no bodyweight gain from Days 1 to 3 postexposure. Reasonable bodyweight development was noted in all female animals during the remainder of the recovery period.

Gross pathology:

With the exception of one instance of dark patches on the lungs, no macroscopic abnormalities were detected amongst animals at necropsy.

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

No deaths occurred in a group of ten rats exposed to a mean achieved atmosphere concentration of 5.64 mg/L for four hours. It was therefore considered that the acute inhalation median lethal concentration (4 hr LC50) of Complexation products of sodium
tartrate with iron trichloride, in the RccHan™ : WIST strain rat, was greater than 5.64 mg/L.

Executive summary:

Introduction.

A study was performed to assess the acute inhalation toxicity of the test item. The method used was designed to be compatible with that described in the OECD Guidelines for Testing of Chemicals (2009) No. 403 "Acute Inhalation Toxicity" and with Method B2 (Inhalation) of Commission Regulation (EC) No. 440/2008.

Methods.

A group of ten RccHan™ : WIST strain rats (five males and five females) was exposed to an aerosol atmosphere. The animals were exposed for four hours using a nose only exposure system, followed by a fourteen day observation period.

Results.

The mean achieved atmosphere concentration was as follows:

Atmosphere Concentration

Mean Achieved (mg/L) 5.64

Standard Deviation 0.71

Nominal (mg/L) 18.5

The characteristics of the achieved atmosphere were as follows:

Mean Achieved Atmosphere Concentration (mg/L) 5.64

Mean Mass Median Aerodynamic Diameter (µM) 2.47

Inhalable Fraction (% < 4 µM) 77.2

Geometric Standard Deviation 1.92

Clinical Observations.

No deaths occured. Common abnormalities noted during the study included increased respiratory rate, hunched posture, pilo-erection and wet fur. From Days 5 to 7 post-exposure the animals recovered and all animals in the study appeared normal after day 7 post-exposure.

Bodyweight.

All males and four female animals exhibited bodyweight losses on the first day post-exposure. All male animals subsequently exhibited reasonable bodyweight gains throughout the remainder of the recovery period. In contrast, three female animals exhibited slight bodyweight losses or showed no bodyweight gain from Days 1 to 3 postexposure. Reasonable bodyweight development was noted in all female animals during the remainder of the recovery period.

Necropsy.

With the exception of one instance of dark patches on the lungs, no macroscopic abnormalities were detected amongst animals at necropsy.

Conclusion.

No deaths occurred in a group of ten rats exposed to a mean achieved atmosphere concentration of 5.64 mg/L for four hours. It was therefore considered that the acute inhalation median lethal concentration (4 hr LC50) of Complexation products of sodium tartrate with iron trichloride, in the RccHan™ : WIST strain rat, was greater than 5.64 mg/L.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 August 2010 - 02 September 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

other: JMAFF Guidelines (2000), including the most recent revisions.

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 10 weeks old) were selected.
- Weight at study initiation: mean males: 305g, mean females:197g
- Fasting period before study: Not applicable
- Housing: Individually housed in labeled Macrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cageenrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom). Acclimatization period was at least 5 days before start of treatment under laboratory conditions. During the acclimatization period the animals were group housed in Macrolon cages (MIV type).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: At least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 - 21.3ºC
- Humidity (%): 46 - 81%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 19 August 2010 - 02 September 2010

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females.
- Type of wrap if used: The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Dressings were removed and the skin cleaned of residual test substance using tap water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (4.517 mL/kg) body weight. Dose volume calculated as (dose level (g/kg) / density (g/mL)) x (100/35), i.e. taking into account the purity of the test substance (35%).

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw/day

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Mortality/Viability: Twice daily.
- Body weights: Days 1 (pre-administration), 8 and 15.
- Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
- Necropsy: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy.
Descriptions of all internal macroscopic abnormalities were recorded.

Statistics:

None

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No effects observed.

Mortality:

No mortality occurred.

Clinical signs:

One male showed flat posture on Day 1. Green staining of the treated skin and/or flank was seen in the animals during the observation period

Body weight:

The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The dermal LD50 value of Complexation products of sodium tartrate with iron trichloride in Wistar rats was established to exceed 2000 mg/kg body weight.

Executive summary:

Assessment of acute dermal toxicity with Complexation products of sodium tartrate with iron trichloride in the rat.

The study was carried out based on the guidelines described in:

OECD No.402 (1987) "Acute Dermal Toxicity"

Commission Regulation (EC) No 440/2008, B3: "Acute Toxicity (Dermal)"

EPA, OPPTS 870.1200 (1998), "Acute Dermal Toxicity"

JMAFF Guidelines (2000), including the most recent revisions.

Complexation products of sodium tartrate with iron trichloride was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No mortality occurred. One male showed flat posture on Day 1. Green staining of the treated skin and/or flank was seen in the animals during the observation period. The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity. No abnormalities were found at macroscopic post mortem examination of the animals. The dermal LD50 value of Complexation products of sodium tartrate with iron trichloride in Wistar rats was established to exceed 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

The oral and dermal LD50 value of the test substance was > 2000 mg/kg body weight. The 4 hr LC50 was > 5.64 mg/L. No mortality occurred and no effects were observed. Therefore classification and labeling is not warranted.